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Shrestha, B. R.

Publications and source records attributed to Shrestha, B. R..

2 recordsLinked to original sources

Large-scale annotated dataset for cochlear hair cell detection and classification

Our sense of hearing is mediated by cochlear hair cells, localized within the sensory epithelium called the organ of Corti. There are two types of hair cells in the cochlea, which are organized in one row of inner hair cells and three rows of outer hair cells. Each cochlea contains a few thousands of hair cells, and their survival is essential for our perception of sound because they are terminally differentiated and do not regenerate after insult. It is often desirable in hearing research to quantify the number of hair cells within cochlear samples, in both pathological conditions, and in response to treatment. However, the sheer number of cells along the cochlea makes manual quantification impractical. Machine learning can be used to overcome this challenge by automating the quantification process but requires a vast and diverse dataset for effective training. In this study, we present a large collection of annotated cochlear hair-cell datasets, labeled with commonly used hair-cell markers and imaged using various fluorescence microscopy techniques. The collection includes samples from mouse, human, pig and guinea pig cochlear tissue, from normal conditions and following in-vivo and in-vitro ototoxic drug application. The dataset includes over 90,000 hair cells, all of which have been manually identified and annotated as one of two cell types: inner hair cells and outer hair cells. This dataset is the result of a collaborative effort from multiple laboratories and has been carefully curated to represent a variety of imaging techniques. With suggested usage parameters and a well-described annotation procedure, this collection can facilitate the development of generalizable cochlear hair cell detection models or serve as a starting point for fine-tuning models for other analysis tasks. By providing this dataset, we aim to supply other groups within the hearing research community with the opportunity to develop their own tools with which to analyze cochlear imaging data more fully, accurately, and with greater ease.

neuroscience↗

Regulation of Auditory Sensory Neuron Diversity by Runx1

Functional heterogeneity among sensory neurons is a cardinal property of the vertebrate auditory system, yet it is not known how this heterogeneity is established to ensure proper encoding of sound. Here, we show that the transcription factor Runx1 controls the composition of molecularly and physiologically diverse sensory neurons (Ia, Ib, Ic) in the murine cochlea, which collectively encode a wide range of sound intensities. Runx1 is enriched in Ib and Ic spiral ganglion neuron (SGN) precursors by late embryogenesis. Loss of Runx1 from embryonic SGNs (Runx1CKO) shifted the balance of subtype identities without affecting neuron number, with more SGNs taking on Ia identities at the expense of Ib/Ic identities, as shown by single cell RNA-sequencing. This conversion was more complete for genes linked to neuronal function than for those related to connectivity. Accordingly, although synaptic position did not change, synapses in the Ib/Ic location took on Ia-like properties. Suprathreshold responses to sound were enhanced in the auditory nerve of Runx1CKO mice, confirming an expansion of neurons behaving functionally like Ia SGNs. Fate-mapping experiments further showed that deletion of Runx1 shortly after birth also redirected Ib and Ic SGNs towards Ia identity, indicating that SGN subtype identities remain plastic postnatally. Altogether, these findings show that diverse neuronal identities essential for normal auditory stimulus coding arise in a hierarchical fashion that remains malleable during postnatal development.

neuroscience↗